Impaired Cholinergic Excitation of Prefrontal Attention Circuitry in the TgCRND8 Model of Alzheimer's Disease.

摘要: Attention deficits in Alzheimer's disease can exacerbate its other cognitive symptoms, yet relevant disruptions of key prefrontal circuitry are not well understood. Here, the TgCRND8 mouse model this neurological disorder, we demonstrate and characterize a disruption cholinergic excitation major corticothalamic layer cortex, which modulation by acetylcholine is essential for optimal attentional function. Using electrophysiology with concurrent multiphoton imaging, show that 6 pyramidal cells unable to sustain same extent as their nontransgenic littermate controls, result excessive activation calcium-activated hyperpolarizing conductances. We report be improved cortex pharmacological blockade SK channels, suggesting novel target treatment dysfunction disease. SIGNIFICANCE STATEMENT accompanied attention symptoms. In brain slices demonstrate, characterize, rescue impaired neurons performance. particular, potassium conductance disrupts normalizes responses. These findings point potential disease.